Interferon (IFN) was approved by the U.S. Food and Drug Administration on June 5, 1986. As the first biotherapeutic approved, IFN-alpha paved the way for development of many other cytokines and growth factors. Nevertheless, we have just touched the surface of understanding the multitude of human IFNs. This paper reviews the history of the purification of human leukocyte IFN and key aspects of our current state of knowledge of human interferon alpha genes, proteins, and receptors.